RESUMO
OBJECTIVE: To evaluate the quality of existing clinical practice guidelines for headache management and their main recommendations. BACKGROUND: Evidence-based clinical practice guidelines have been developed to support the clinical decision-making. However, to achieve this goal, the quality of these guidelines must be ensured. METHODS: A systematic search for clinical practice guidelines for headache management was conducted in the PubMed database, in websites of known guideline developers and in websites of known headache associations. The quality appraisal was performed through the Appraisal of Guidelines for Research and Evaluation II method. RESULTS: Twelve guidelines were evaluated. The domains of rigor of development, applicability, and editorial independence, which most influence the overall quality of guidelines, had the lowest average scores and the highest standard deviation rates (61% ± 23; 37% ± 20; 53% ± 31). The main recommendations regarding medication use for acute treatment of episodic tension-type headache and migraine in adult patients consisted of paracetamol, acetylsalicylic acid, and other nonsteroidal anti-inflammatory drugs in all guidelines. CONCLUSIONS: The statistical results indicate that the appraised guidelines have room for both individual and collective improvement. In addition, there is a well-established medication recommendation pattern among all guidelines evaluated.
Assuntos
Transtornos de Enxaqueca , Cefaleia do Tipo Tensional , Adulto , Cefaleia/terapia , Humanos , Transtornos de Enxaqueca/terapia , Guias de Prática Clínica como AssuntoRESUMO
The subcutaneous air pouch is an in vivo model that can be used to study the components of acute and chronic inflammation, the resolution of the inflammatory response, the oxidative stress response, and potential therapeutic targets for treating inflammation. Injection of irritants into an air pouch in rats or mice induces an inflammatory response that can be quantified by the volume of exudate produced, the infiltration of cells, and the release of inflammatory mediators. The model presented in this unit has been extensively used to identify potential anti-inflammatory drugs.
Assuntos
Carragenina/farmacologia , Mediadores da Inflamação/metabolismo , Inflamação/induzido quimicamente , Pele/patologia , Animais , Modelos Animais de Doenças , Exsudatos e Transudatos/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Ratos , Pele/efeitos dos fármacos , Pele/metabolismoRESUMO
Previous work from our group showed that intrathecal (i.t.) administration of substances such as glutamate, NMDA, or PGE(2) induced sensitization of the primary nociceptive neuron (PNN hypernociception) that was inhibited by a distal intraplantar (i.pl.) injection of either morphine or dipyrone. This pharmacodynamic phenomenon is referred to in the present work as "teleantagonism". We previously observed that the antinociceptive effect of i.t. morphine could be blocked by injecting inhibitors of the NO signaling pathway in the paw (i.pl.), and this effect was used to explain the mechanism of opioid-induced peripheral analgesia by i.t. administration. The objective of the present investigation was to determine whether this teleantagonism phenomenon was specific to this biochemical pathway (NO) or was a general property of the PNNs. Teleantagonism was investigated by administering test substances to the two ends of the PNN (i.e., to distal and proximal terminals; i.pl. plus i.t. or i.t. plus i.pl. injections). We found teleantagonism when: (i) inhibitors of the NO signaling pathway were injected distally during the antinociception induced by opioid agonists; (ii) a nonselective COX inhibitor was tested against PNN sensitization by IL-1beta; (iii) selective opioid-receptor antagonists tested against antinociception induced by corresponding selective agonists. Although the dorsal root ganglion seems to be an important site for drug interactions, the teleantagonism phenomenon suggests that, in PNNs, a local sensitization spreads to the entire cell and constitutes an intriguing and not yet completely understood pharmacodynamic property of this group of neurons.
Assuntos
Analgésicos Opioides/farmacologia , Morfina/farmacologia , Nociceptores/efeitos dos fármacos , Dor/tratamento farmacológico , Células Receptoras Sensoriais/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Dinoprostona/farmacologia , Dopamina/farmacologia , Interações Medicamentosas , Inibidores Enzimáticos/farmacologia , Indometacina/farmacologia , Interleucina-1beta/farmacologia , Masculino , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Óxido Nítrico/metabolismo , Oxidiazóis/farmacologia , Dor/metabolismo , Pirrolidinas/farmacologia , Quinoxalinas/farmacologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , ômega-N-Metilarginina/farmacologiaRESUMO
OBJECTIVE: The present study describes intercalated disc remodeling under both protein expression and structural features in experimental severe sepsis induced by cecal ligation and puncture in mice. DESIGN: Controlled animal study. SETTING: University research laboratory. SUBJECTS: Male C57BL/6 mice. INTERVENTIONS: Mice were submitted to moderate and severe septic injury by cecal ligation and puncture. MEASUREMENT AND MAIN RESULTS: Severe septic injury was accompanied by a large number of bacteria in the peritoneal cavity and blood, high levels of tumor necrosis factor-alpha, and monocyte inflammatory protein-1alpha in the septic focus and serum, marked hypotension, and a high mortality rate. Western blot analysis and immunofluorescence showed a marked decrease of key gap and adherens junction proteins (connexin43 and N-cadherin, respectively) in mice submitted to severe septic injury. These changes may result in the loss of intercalated disc structural integrity, characterized in the electron microscopic study by partial separation or dehiscence of gap junctions and adherens junctions. CONCLUSIONS: Our data provide important insight regarding the alterations in intercalated disc components resulting from severe septic injury. The intercalated disc remodeling under both protein expression and structural features in experimental severe sepsis induced by cecal ligation and puncture may be partly responsible for myocardial depression in sepsis/septic shock. Although further electrophysiological studies in animals and humans are needed to determine the effect of these alterations on myocardial conduction velocity, the abnormal variables may emerge as therapeutic targets, and their modulation might provide beneficial effects on future cardiovascular outcomes and mortality in sepsis.